Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.
Animals ; Antineoplastic Agents ; therapeutic use ; Drug Carriers ; Energy Metabolism ; Glucose ; analogs & derivatives ; chemistry ; metabolism ; therapeutic use ; Glycoconjugates ; chemistry ; therapeutic use ; Glycolysis ; Glycosides ; chemistry ; Humans ; Ifosfamide ; analogs & derivatives ; chemistry ; therapeutic use ; Neoplasms ; diagnosis ; drug therapy ; metabolism ; Nitroimidazoles ; chemistry ; Radiation-Sensitizing Agents ; chemistry

The abnormal glycans expressing on the surface of tumor cells are good targets to develop carbohydrate-based anti-cancer vaccines. However, one of the major problems is that carbohydrate antigens possess weak immunogenicity. This review summarizes the recent efforts to overcome this problem: glycoconjugates produced by coupling the carbohydrate antigens and proper carrier proteins improve their immunogenicity, many glycoconjugates have entered clinical trials; the vaccines become chemically well-defined when coupling the carbohydrate antigens with a T-cell peptide epitope and an immunostimulant to form fully synthetic multi-component glycoconjugate vaccines; the modification of carbohydrate antigens in combination with the technology of metabolic oligosaccharide engineering of tumor cells induces a strong immune response; and the fact that the antibodies elicited against the unnatural carbohydrate antigens can recognize the native carbohydrate antigens on tumor cells provides a new promising strategy for the development of anti-cancer vaccines.
Animals ; Antigens, Tumor-Associated, Carbohydrate ; chemistry ; immunology ; Cancer Vaccines ; chemical synthesis ; chemistry ; immunology ; therapeutic use ; Carbohydrates ; chemistry ; immunology ; Epitopes, T-Lymphocyte ; chemistry ; immunology ; Glycoconjugates ; chemistry ; immunology ; Humans ; Immune Tolerance ; Metabolic Engineering ; methods ; Neoplasms ; prevention & control ; therapy ; Oligosaccharides ; chemistry

Histochemical patterns of lectin binding during development of the rat vomeronasal organ (VNO) were studied to determine whether glycoconjugates are differently expressed after birth. Three types of lectins, Dolichos biflorus agglutinin (DBA), wheat germ agglutinin (WGA), and Ulex europaeus agglutinin I (UEA-I), were studied histochemically in the rat VNO at various stages post-birth: postnatal days 1 and 7, the preweaning period (4 weeks after birth), and at sexual maturity (8 weeks after birth). The free border of the vomeronasal sensory epithelium was positive for both WGA and UEA-I in rats of all ages; whereas, VNO receptor cells and supporting cells were positive only for both WGA and UEA-I from 4 weeks after birth. DBA reactivity was detected in the free border but less so in receptor cells and supporting cells. WGA and UEA-I, but not DBA, showed similar patterns in various ages. In the Jacobson's gland, WGA, UEA-I and DBA were detected in some acini from 4 weeks after birth but not at postnatal days 1 or 7. Collectively, reactivity for three lectins, WGA, UEA-I and DBA, increased in receptor cells and gland acini during postnatal development, possibly contributing to the enhanced chemoreception in rats.
Animals ; Dolichos ; Epithelium ; Glycoconjugates ; Lectins ; Parturition ; Plant Lectins ; Rats ; Triticum ; Ulex ; Vomeronasal Organ

The present study was carried out to investigate the glycoconjugate properties of the nasal mucosa in the rat after inhalation of formaldehyde. Sprague-Dawley male rats were inhalated 30 ppm formaldehyde for 3 times with 3 hours exposure. The olfactory and respiratory mucosa in the nasal mucosa were taken from the animals on 3, 6,9 days and 2, 3, 4, 5 weeks after inhalation of formaldehyde. The properties of glycoconjugate of the olfactory and respiratory mucosa were investigated using nine biotinylated lectins (PSA, UEA I, PHA-L, BSL I, PNA, MAL I, DBA, BSL II or sWGA). In experimental groups, the degenerative changes of the olfactory epithelium were observed until 3 weeks after inhalation of formaldehyde, but the respiratory epithelium was no change. In control group, the olfactory cells in the olfactory epithelium reacted with PSA, UEA I, PNA, DBA, BSL II, sWGA, and the supporting cells reacted with PSA, PHA-L, PNA, MAL I, DBA, BSL II, sWGA, and Bowman's glands reacted with all the lectins. In experimental groups, the olfactory cells reacted with UEA I, DBA, and the supporting cells reacted with PHA-L, MAL I, DBA, UEA I, and the positive reaction of Bowman's glands was increased. In control group, the goblet cells in the respiratory epithelium reacted with UEA I, MAL I, and the ciliated columnar cells reacted with PSA, UEA I, PHA-L, BSL I, DBA, BSL II, sWGA, and the septal nasal glands reacted with all the lectins except UEA I. In experimental groups, the goblet cells reacted with UEA I, MAL I and PNA. Conclusively, the olfactory mucosa was shown a lot of changes in the properties of glycoconjugates following inhalation of formaldehyde, but respiratory mucosa was shown feeble change. These results suggest that there were different sugar residues of glycoconjugate in the olfactory and respiratory mucosa following inhalation of formaldehyde, respectively.
Animals ; Formaldehyde ; Glycoconjugates ; Goblet Cells ; Humans ; Inhalation ; Lectins ; Male ; Nasal Mucosa ; Olfactory Mucosa ; Phytohemagglutinins ; Rats ; Respiratory Mucosa ; Wheat Germ Agglutinins

To investigate changes of glycoconjugates (GC) on the duodenal mucosa of Korean chipmunks (Tamias sibiricus) after cold-treatment, chipmunks were maintained in cold conditions (6 C) for 3, 5 or 9 months in an attempt to mimic conditions occurring during seasonal hibernation. Most chipmunks were active as before until 3 months in the cold room and since then were hibernated. Although there was significant decrease in neutral GC in cold-treated chipmunks compared with warm chipmunks, acid GC changed little. As for histochemical properties of acid GC in the duodenum, the cold-treated chipmunk showed some differences, such as appearance of villus goblet cells which contained the mixture of sulfated and nonsulfated GC. The affinities for all lectins used in this study were shown in the columnar cells of the duodenal villus and crypt, more intensive DBA, SBA, PNA, BSL-1, RCA-1 and sWGA affinities were demonstrated in the Golgi zone of columnar cells. These affinities decreased in the cold-treated groups, especially in the Golgi zone of columnar cells. The affinities with DBA, RCA-1, sWGA and BSL-1 was demonstrated in the goblet cells of the duodenum, but these affinities except DBA decreased in the cold-treated chipmunks. All lectin affinities except UEA-1 detected in duodenal gland, but cold-treatment induced a decrease of these affinities. The changes in amount and properties of GC in the present experimental model for hibernation may be due to the different intestinal environment associated with food intake. However, the present experimental model for hibernation, especially 9 months cold-treated chipmunks, stills need to be demonstrated during seasonal hibernation in the wild.
Duodenum ; Eating ; Glycoconjugates* ; Goblet Cells ; Hibernation ; Lectins ; Models, Theoretical ; Mucous Membrane* ; Sciuridae* ; Seasons

BACKGROUND: Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. METHODS: Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in 300microliter PBS (LPS group). Sterile PBS (300microliter) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. RESULTS: The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. CONCLUSION: Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.
Animals ; Bacterial Infections ; Coloring Agents ; Epidermal Growth Factor* ; Epithelium ; Glycoconjugates ; Goblet Cells ; Hyperplasia ; Inflammation ; Leukocytes ; Lung ; Matrix Metalloproteinases ; MMPI ; Mucins ; Mucus* ; Neutrophils* ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor* ; Trachea

BACKGROUND: Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. METHODS: Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in 300microliter PBS (LPS group). Sterile PBS (300microliter) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. RESULTS: The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. CONCLUSION: Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.
Animals ; Bacterial Infections ; Coloring Agents ; Epidermal Growth Factor* ; Epithelium ; Glycoconjugates ; Goblet Cells ; Hyperplasia ; Inflammation ; Leukocytes ; Lung ; Matrix Metalloproteinases ; MMPI ; Mucins ; Mucus* ; Neutrophils* ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor* ; Trachea

OBJECTIVE: Lectins are cell-agglutinating and sugar specific proteins or glycoproteins of non-immune origin that precipitate glycoconjugates having saccharides of appropriate complementarity. Because of these properties, plant lectins have been used to help characterize the carbohydrate moieties of glycoproteins in the zona pellucida (ZP) of several mammalian species including pigs. Treatment of oocytes with various lectins blocks sperm binding to the ZP in various mammalian species. This study was undertaken to examine the distribution of sugar residues in the ZP of pig oocytes matured in vitro and the ability of spermatozoa to bind to ZP and in vitro penetration in oocytes treated with fluorescein isothiocyanate (FITC)-labelled lectins. MATERIALS AND METHODS: The lectins of Banderiaea simplicifolia (BS-II, bind to beta-D-Nacetylglucosamine), Canavalin ensiformis (Con A, bind to alpha-D-Mannose), Lens culinaris (LCA, bind to alpha-D-Mannose), Ricinus communis (RCA-I, bind to beta-D-Galactose) and Ulex europaeus (UEA-I, bind to alpha-L-Fucose) were examined for spermatozoa penetration, binding capacity to ZP and distribution of lectins. RESULTS: The penetration rates were significantry (p<0.05) higher in control oocytes (63%) than those treated with all lectins, but penetration rates (40~49%) were simililar in group treated with lectins. The incidence of monospermy was similar in oocytes untreated and UEA-I, but it was higher in oocytes treated with BS-II, Con A, RCA-I and LCA. The porcine oocytes cultured for 48 h in TC-199 medium were freed from cumulus cells and treated for 30 min with fluorescein isothiocyanate-labelled lectins. When examined under fluorescein illumination, higher (p<0.001) proportions of oocytes showed fluorescein of zona pellucida after treatment with Con A (93%), LCA (93%) and RCA-I (100%) than BS-II (37%) and UEA-I (50%). All of the oocytes treated with RCA-I exhibited strong fluorescein in the outer region of the zona pellucida while those treated with LCA exhibited strong fluorescein throughout the zona pellucida. BS-II bounded mainly to the outer region and UEA-I bounded mainly to the inner region of the zona pellucida, with either strong or weak fluorescein. At 120 min after insemination in vitro, fewer spermatozoa were bound to the zona pellucida of the oocytes treated with BS-II, Con-A and RCA-I. Of the lectins, Con A most inhibited sperm binding. CONCLUSIONS: These results suggest that beta-D-Galactose residues in the porcine zona pellucida may act as primary sperm receptors and inducers of the sperm acrosome reaction and these sugar residues may be involved in the block to polyspermy.
Acrosome Reaction ; Cumulus Cells ; Fluorescein ; Glycoconjugates ; Glycoproteins ; Herpes Zoster* ; Incidence ; Insemination ; Lectins* ; Lens Plant ; Lighting ; Oocytes ; Plant Lectins ; Ricinus ; Sperm-Ovum Interactions ; Spermatozoa ; Swine ; Ulex ; Zona Pellucida*

The experiments of this study was performed to investigate the effects of sulfur dioxide on the changes of glycoconjugates of respiratory system of the rat. Sprague -Dawley male rats weighing about 200 ~250g were divided into a control group and SO2 exposed groups. Again SO2 exposed groups were divided into 10 ppm, 25 ppm, 50 ppm, 100 ppm and 200 ppm subgroups according to concentrations of SO2 and each SO2 exposed groups were divided into 1, 3 and 6 hours groups. For the histological changes, H -E(hematoxylin -eosin) and PAS(periodic acid Schiff) staining were used and to investigate the change of sugar residues of glycoconjugates, biotinylated lectins(DBA, SBA, PNA, BSL -1, sWGA, UEA -1, LCA and Con A) were applied. Generally, the effects of SO2 on the rat nasal respiratory region were more serious at the high concentrations. Moreover, as the exposed time was longer even at the low concentrations, the effects of SO2 were similar to those of high concentration. Compared with all SO2 concentrations, the longer exposed time was, the more serious the effects of SO2 were. In the SO2 exposed groups the binding of PNA, RCA -1 and UEA -1 of cilia in the nasal septal respiratory epithelium tended to increase in the 10 ppm and 25 ppm SO2 exposed groups but it tended to decrease in the 100 ppm and 200 ppm SO2 exposed groups. In the cytoplasm of columnar cells of nasal septal respiratory epithelium, Con A binding increased in all the SO2 exposed groups. In the goblet cells DBA, SBA, PNA, RCA -1 and UEA -1 binding increased remarkably in the 50 ppm SO2 exposed groups but it decreased largely or disappeared in the 100 ppm and 200 ppm SO2 exposed groups. The binding of SBA, PNA, BSL -1, UEA -1 and Con A in the intraepithelial mucous cells which were not detected in the control group, increased in the 25 ppm and 50 ppm SO2 exposed groups while it tended to decrease in the 100 ppm and 200 ppm SO2 exposed groups. The binding of sWGA increased according to the concentrations of SO2 were higher and exposed times were longer. In the superior nasal septal gland, the binding of PNA increased in the 50 ppm and 100 ppm SO2 exposed groups and that of Con A increased in the 25 ppm and 50 ppm SO2 exposed groups. In the inferior nasal septal gland, except for LCA, the binding of the other lectins increased remarkably in the 25 ppm and 50 ppm SO2 exposed groups but it tended to decrease in the 100 ppm and 200 ppm SO2 groups. In the mucous duct cells, the reaction of PNA and RCA -1 increased compared with that of the control group. And the reaction of BSL -1 and UEA -1 increased in the lower concentrations of 50 ppm SO2 exposed group but it decreased in the 100 ppm and 200 ppm SO2 exposed groups. The binding of Con A increased in the 25 ppm and 50 ppm SO2 exposed groups. Consequently, from the results above mentioned that SO2 affected serious changes on glycoconjugates metabolism in the nasal cavity.
Animals ; Cilia ; Cytoplasm ; Glycoconjugates* ; Goblet Cells ; Humans ; Lectins ; Male ; Metabolism ; Nasal Cavity* ; Rats* ; Respiratory Mucosa* ; Respiratory System ; Sulfur Dioxide

BACKGROUND: In the pathogenesis of ulcerative colitis, a defective mucosal barrier to luminal antigens is currently under consideration, and alterations in mucin structure and lectin binding may play an important role in the defect of mucosal barrier. It is also, suggested that the differences in clinical manifestation and complication of ulcerative colitis are associated with the change in glycosylation of colonic mucus glycoconjugates. This study was performed in order to investigate the histochemical properties of the mucin in korean ulcerative colitis. METHODS: The histochemical staining (HID-AB, mild PAS, PBT-KOH-PAS) and the binding of lectin (PNA, DBA, UEA-1, RCA-1, WGA, with avidin-biotin peroxidase complex method) to mucin glycoconjugates were analyzed in paraffin-embedded tissue sections obtained from 14 normal colons and 20 ulcerative colitis. RESULTS: In the ulcerative colitis, number of goblet cell and amount of mucin were decreased, but the expression of its sulphomucin was consistently predominant and strong like normal colon. The expression of N-acetylated sialomucin was more common in the ulcerative colitis(80%) than normal colon(50%) and its grading mildly increased in ulcerative colitis. The expression of O-acetylated sialomucin was present in all cases of normal colon and its staining grade decreased in the ulcerative colitis. Compared to normal colonic mucosa, ulcerative colitis showed the increase in PNA and DBA binding in the supranuclear cytoplasm, the decrease in DBA and RCA-1 binding in the goblet cells, and no change in UEA-1 and WGA binding in both. In the ulcerative colitis, the increase in PNA and DBA binding was mild in the supranuclear cytoplasm and the expression of DBA and RCA-1 binding in goblet cells variably decreased. CONCLUSIONS: This study demonstrates the changes in the mucosal glycoconjugates between the ulcerative colitis and normal colon. The mucinous glycoconjugate expression of korean ulcerative colitis are different from that of western patients. There may be a genetic, racial variation in the glycoconjugate, which may also play a part in the differences in pathogenesis, clinical manifestation, and complication of ulcerative colitis.
Colitis ; Colitis, Ulcerative* ; Colon ; Cytoplasm ; Glycoconjugates ; Glycosylation ; Goblet Cells ; Humans ; Lectins ; Mucins* ; Mucous Membrane* ; Mucus ; Peroxidase ; Phenobarbital ; Sialomucins ; Ulcer*